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Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma

Abstract

Harmine hydrochloride (Har-hc), a derivative from Harmine which is a natural extractive from plants, has been considered for treatment of kinds of cancers and cerebral diseases. In this study, we found that Har-hc clearly decreased cell viability, induced apoptosis and inhibited Akt phosphorylation in glioblastoma cell lines. Moreover, Har-hc had the ability to inhibit self-renewal and promote differentiation of glioblastoma stem like cells (GSLCs) accompanied by inhibition of Akt phosphorylation. Especially, we demonstrated that Har-hc inhibited neurosphere formation of human primary GSLCs. In vivo test also confirmed Har-hc decreased the tumorigenicity of GSLCs. Thus we conclude that Har-hc has potent anti-cancer effects in glioblastoma cells, which is at least partially via inhibition of Akt phosphorylation. Administration of Har-hc may act as a new approach to glioblastoma treatment.

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Acknowledgments

This study was supported by National Natural Science Foundations of China (30901533, 81172388 to Yaohua Liu and 30973078, 81272788 to Shiguang Zhao).

Conflict of interest

The authors have declared that no competing interests exist.

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Correspondence to Shiguang Zhao.

Additional information

Huailei Liu, Dayong Han and Yaohua Liu contributed equally to this work.

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Liu, H., Han, D., Liu, Y. et al. Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma. J Neurooncol 112, 39–48 (2013). https://doi.org/10.1007/s11060-012-1034-x

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  • DOI: https://doi.org/10.1007/s11060-012-1034-x

Keywords

  • Harmine hydrochloride
  • Glioblastoma
  • Akt
  • Glioblastoma stem-like cells
  • Neurosphere